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. 2014 Jun 6;9(6):1059-65.
doi: 10.2215/CJN.11041013. Epub 2014 Apr 17.

Association of a polymorphism in a gene encoding a urate transporter with CKD progression

Alessandra Testa  1 , Francesca Mallamaci  1 , Belinda Spoto  1 , Anna Pisano  1 , Maria Cristina Sanguedolce  1 , Giovanni Tripepi  1 , Daniela Leonardis  1 , Carmine Zoccali  2
Affiliations

Association of a polymorphism in a gene encoding a urate transporter with CKD progression

Alessandra Testa et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: Hyperuricemia predicts a high risk for CKD progression but there is no large clinical trial in humans indicating that this relationship is causal in nature. The rs734553 single-nucleotide polymorphism (SNP) of the GLUT9 urate transporter gene was strongly associated with uric acid (UA) levels in a large meta-analysis VSports手机版. .

Design, setting, participants, & measurements: This prospective study adopted the Mendelian randomization approach. The rs734553 SNP was used as an instrumental variable to investigate the relationship between UA and renal outcomes in a cohort of 755 patients with CKD who were enrolled between October 18, 2005, and October 2, 2008. The association between the polymorphism and UA was preliminary confirmed in a series of 211 healthy volunteers enrolled between January 1, 2001, and July 12, 2011, from the same geographic area as the patients with CKD. The study end point was a composite renal-end point (i V体育安卓版. e. , >30% decrease in the GFR, dialysis, or transplantation). Patients were followed up for a median of 36 months. .

Results: In healthy individuals, serum UA levels were highest in homozygotes for the T allele (risk allele), intermediate in heterozygotes for the same allele, and lowest in those without the risk allele (P<0. 001), but no such relationship was found in patients with CKD. In the CKD cohort, homozygotes (TT) and heterozygotes (GT) for the risk allele had a 2. 35 times higher risk (hazard ratio, 2. 35; 95% confidence interval, 1. 25 to 4. 42; P=0. 008) of CKD progression. The risk for CKD progression by rs734553 remained unmodified in analyses adjusting for proteinuria, GFR, and other classical and CKD-peculiar risk factors. V体育ios版.

Conclusions: A GLUT9 polymorphism, which is strongly associated with serum UA levels in healthy individuals of the general population with normal renal function, holds a strong predictive power for CKD progression. These findings are compatible with the hypothesis that the link between UA and CKD progression is causal in nature. VSports最新版本.

Keywords: CKD progression; epidemiology; polymorphisms; uric acid. V体育平台登录.

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Figures

Figure 1.
Figure 1.
Uric acid levels and GLUT9 genotypes divided according to dominant and codominant models in healthy individuals. Data are expressed as mean (and SD) and P value.
Figure 2.
Figure 2.
Cumulative events-free survival (Kaplan–Meyer curves) for renal events in GG and GT+TT patients. The comparison between the two groups was made by the log-rank test. The table under the x axis indicates the number of patients at risk at relevant time points.
See this image and copyright information in PMC

References

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